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Circulation Oct 2023In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory... (Review)
Review
2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, β-adrenergic receptor antagonists (also known as β-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.
Topics: Humans; Adrenergic beta-Antagonists; American Heart Association; Benzodiazepines; Cardiopulmonary Resuscitation; Digoxin; Heart Arrest; United States
PubMed: 37721023
DOI: 10.1161/CIR.0000000000001161 -
Environmental Health Perspectives Oct 2023Widespread insecticide exposure might be a risk factor for neurodevelopment of our children, but few studies examined the mixture effect of maternal coexposure to...
BACKGROUND
Widespread insecticide exposure might be a risk factor for neurodevelopment of our children, but few studies examined the mixture effect of maternal coexposure to organophosphate insecticides (OPPs), pyrethroids (PYRs), and neonicotinoid insecticides (NNIs) during pregnancy on child neurodevelopment, and critical windows of exposure are unknown.
OBJECTIVES
We aimed to evaluate the association of prenatal exposure to multiple insecticides with children's neurodevelopment and to identify critical windows of the exposure.
METHODS
Pregnant women were recruited into a prospective birth cohort study in Wuhan, China, from 2014-2017. Eight metabolites of OPPs (mOPPs), three metabolites of PYRs (mPYRs), and nine metabolites of NNIs (mNNIs) were measured in 3,123 urine samples collected at their first, second, and third trimesters. Children's neurodevelopment [mental development index (MDI) and psychomotor development index (PDI)] was assessed using the Bayley Scales of Infant Development at 2 years of age (). Multivariate linear regression models, generalized estimating equation models, and weighted quantile sum (WQS) regression were used to estimate the association between the insecticide metabolites and Bayley scores. Potential sex-specific associations were also examined.
RESULTS
Single chemical analysis suggested higher urinary concentrations of some insecticide metabolites at the first trimester were significantly associated with lower MDI and PDI scores, and the associations were more prominent among boys. Each 1-unit increase in ln-transformed urinary concentrations of two mOPPs, 3,5,6-trichloro-2-pyridinol and 4-nitrophenol, was associated with a decrease of 3.16 points [95% confidence interval (CI): , ] and 3.06 points (95% CI: , ) respectively in boys' MDI scores. Each 1-unit increase in that of -3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (-DCCA; an mPYR) was significantly associated with a decrease of 2.24 points (95% CI: , ) in boys' MDI scores and 1.90 points (95% CI: , ) in boys' PDI scores, respectively. Significantly positive associations of maternal urinary biomarker concentrations [e.g., dimethyl phosphate (a nonspecific mOPP) and desmethyl-clothianidin (a relatively specific mNNI)] with child neurodevelopment were also observed. Using repeated holdout validation, a 1-quartile increase in the WQS index of the insecticide mixture (in the negative direction) at the first trimester was significantly associated with a decrease of 3.02 points (95% CI: , ) in MDI scores among the boys, and -DCCA contributed the most to the association (18%).
CONCLUSIONS
Prenatal exposure to higher levels of certain insecticides and their mixture were associated with lower Bayley scores in children, particularly in boys. Early pregnancy may be a sensitive window for such an effect. Future studies are needed to confirm our findings. https://doi.org/10.1289/EHP12097.
Topics: Male; Infant; Humans; Child; Female; Pregnancy; Insecticides; Pyrethrins; Prospective Studies; Cohort Studies; Prenatal Exposure Delayed Effects; Organophosphates; Child Development; Neonicotinoids; Maternal Exposure
PubMed: 37856202
DOI: 10.1289/EHP12097 -
ACS Organic & Inorganic Au Aug 2023Organophosphorus nerve agents (OPAs) are a toxic class of synthetic compounds that cause adverse effects with many biological systems. Development of methods for...
Organophosphorus nerve agents (OPAs) are a toxic class of synthetic compounds that cause adverse effects with many biological systems. Development of methods for environmental remediation and passivation has been ongoing for years. However, little progress has been made in therapeutic development for exposure victims. Given the postexposure behavior of OPA materials in enzymes such as acetylcholinesterase (AChE), development of electrophilic compounds as therapeutics may be more beneficial than the currently employed nucleophilic countermeasures. In this report, we present our studies with an electrophilic, 16-electron manganese complex (PNP)Mn(CO) () and the nucleophilic hydroxide derivative (PNP)Mn(CO)(OH) (). The reactivity of with phosphorus acids and the reactivity of with the P-F bond of diisopropylfluorophosphate (DIPF) were studied. The role of water in both nucleophilic and electrophilic reactivity was investigated with the use of O-labeled water. Promising results arising from reactions of both and with organophosphorus substrates are reported.
PubMed: 37545657
DOI: 10.1021/acsorginorgau.3c00003 -
Chemosphere Oct 2023Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic... (Review)
Review
Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic evidence in 2015. Since then, numerous studies of glyphosate and its formulations (GBF) have emerged. These studies can be evaluated for cancer hazard identification with the newly described ten key characteristics (KC) of carcinogens approach. Our objective was to assess all in vivo, ex vivo, and in vitro mechanistic studies of human and experimental animals (mammals) that compared exposure to glyphosate/GBF with low/no exposure counterparts for evidence of the ten KCs. A protocol with our methods adhering to PRISMA guidelines was registered a priori (INPLASY202180045). Two blinded reviewers screened all in vivo, ex vivo, and in vitro studies of glyphosate/GBF exposure in humans/mammals reporting any KC-related outcome available in PubMed before August 2021. Studies that met inclusion criteria underwent data extraction conducted in duplicate for each KC outcome reported along with key aspects of internal/external validity, results, and reference information. These data were used to construct a matrix that was subsequently analyzed in the program R to conduct strength of evidence and quality assessments. Of the 2537 articles screened, 175 articles met inclusion criteria, from which we extracted >50,000 data points related to KC outcomes. Data analysis revealed strong evidence for KC2, KC4, KC5, KC6, KC8, limited evidence for KC1 and KC3, and inadequate evidence for KC7, KC9, and KC10. Notably, our in-depth quality analyses of genotoxicity (KC2) and endocrine disruption (KC8) revealed strong and consistent positive findings. For KC2, we found: 1) studies conducted in humans and human cells provided stronger positive evidence than counterpart animal models; 2) GBF elicited a stronger effect in both human and animal systems when compared to glyphosate alone; and 3) the highest quality studies in humans and human cells consistently revealed strong evidence of genotoxicity. Our analysis of KC8 indicated that glyphosate's ability to modulate hormone levels and estrogen receptor activity is sensitive to both exposure concentration and formulation. The modulations observed provide clear evidence that glyphosate interacts with receptors, alters receptor activation, and modulates the levels and effects of endogenous ligands (including hormones). Our findings strengthen the mechanistic evidence that glyphosate is a probable human carcinogen and provide biological plausibility for previously reported cancer associations in humans, such as non-Hodgkin lymphoma. We identified potential molecular interactions and subsequent key events that were used to generate a probable pathway to lymphomagenesis.
Topics: Animals; Humans; Carcinogens; Herbicides; Neoplasms; Lymphoma, Non-Hodgkin; Mammals; Glyphosate
PubMed: 37474029
DOI: 10.1016/j.chemosphere.2023.139572